Propranolol inhibits the angiogenic capacity of hemangioma endothelia via blocking β-adrenoceptor in mast cell

Abstract

Background: Propranolol, a non-selective blocker of the β-adrenoceptor (AR), is a first-line treatment for infantile hemangioma (IH). Mast cells have been implicated in the pathophysiology of propranolol-treated hemangioma. However, the function of mast cells remains unclear.

Methods: HMC-1s (Human mast cell line) having been treated with propranolol for 24 h were centrifuged, washed with PBS twice, and maintained in cell culture medium for another 24 h. The supernatants with propranolol which were named as propranolol-treated HMC-1s supernatants were obtained. The expression of cytokines and mediators was examined among HMC-1s dealt with propranolol. HemECs (hemangioma endothelial cells) were co-cultured with propranolol-treated HMC-1s supernatants, and their proliferation and apoptosis were investigated. The autophagic-related protein was examined in HemECs using immunoblot.

Results: In propranolol-treated HMC-1s, the expressions of ADRB1 (β1-AR) and ADRB2 (β2-AR) were reduced by 70% and 60%, respectively, and that of cytokines and mediators were reduced. The proliferation was decreased, but apoptosis and autophagy were induced in HemECs treated with propranolol-treated HMC-1s supernatants. However, propranolol can work well in shRNA-ADRB1 or shRNA-ADRB2 transfected HMC-1s.

Conclusions: Propranolol inhibit the proliferation of HemECs and promote their apoptosis and autophagy through acting on both β1 and β2 adrenoceptor in mast cell.

Impact: Treated with propranolol, β1, and β2 adrenoceptor on human mast cell expression was reduced significantly. After hemangioma endothelial cell treated with the supernatants from propranolol-treated human mast cell, its proliferation was decreased, but apoptosis and autophagy were significantly induced. Propranolol can work well in shRNA-ADRB1 or shRNA-ADRB2 transfected HMC-1s. Mast cells may have a role in the action of propranolol in infantile hemangioma through both β1 and β2 adrenoceptors to inhibit the angiogenic capacity of hemangioma endothelial cells.